Iron deprivation and cancer: a view beginning with studies of monoclonal antibodies against the transferrin receptor.

This review provides a perspective on the potential utility of iron deprivation treatments as components of cancer therapy. The perspective began to develop with investigations of the selective inhibitory effects on lymphocyte activation which were produced by monoclonal antibodies against the transferrin receptor. Those investigations led to the unexpected discovery that such antibodies would produce synergistic inhibition of lymphoid tumor growth in vitro when used in combination with the iron chelator deferoxamine. The perspective was further developed when additional studies in vivo indicated that combination iron deprivation treatment could prevent initial tumor outgrowth and cause regressions of established tumors in the 38C13 murine lymphoma model. The anti-tumor effects were accompanied by significant toxicities, however, and the analysis of the causes of those toxicities is now an important issue. The opportunities and problems which these results present are interpreted in the broader context of currently available information concerning the anti-tumor effects of deferoxamine and gallium nitrate in the pre-clinical and clinical settings, and questions for future research are presented.